Hani Goodarzi
@genophoria.bsky.social
1.8K followers 270 following 180 posts
Core Investigator @ Arc Institute | Associate Professor @ UCSF | {Computational, Systems, Cancer, RNA} biologist | Co-founder @exaibio @vevo_ai
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Reposted by Hani Goodarzi
pauldatlinger.bsky.social
#CELLFIE for CAR T screening—a new mRNA-based platform for screening primary cells. CAR + gRNA library are delivered by lentivirus, CRISPR modifiers as electroporated mRNA. That’s more flexible and effective than existing T cell screening methods. (1/7)
Reposted by Hani Goodarzi
Reposted by Hani Goodarzi
raflynn5.bsky.social
RNA N-glycosylation enables immune evasion and homeostatic efferocytosis by chemically caging acp3U. Excited to report this work lead by Vinnie @vinnieviruses.bsky.social and in collaboration with @vijayrathinam.bsky.social in @nature.com www.nature.com/articles/s41...
genophoria.bsky.social
Go @exai.bio! Looking forward to working with Mike as our incoming CEO and our amazing board members.
exai.bio
exai bio @exai.bio · Jul 23
We’re excited to welcome Michael Nall as CEO and Board Director and new Board Directors - Steve Kafka, PhD, of S32, Dusan Perovic of Two Sigma Ventures and Emir Sandhu, MD, of Blue Venture Fund. Their leadership will be invaluable as we advance our RNA & AI liquid biopsy platform.
Reposted by Hani Goodarzi
fusionconf.bsky.social
Are you currently in the ERE related field & want to find new collaborative opportunities? Join our Chairs @chiappinellilab.bsky.social, @shenhui1986.bsky.social, Ting & Tao at #EREHD25 this Nov!
🎙️Talk Submission extended to 03 Sept
💰Final few $500 grants remaining
Don't Miss out! bit.ly/4eRq9Mp
genophoria.bsky.social
Congratulations... amazing!
Reposted by Hani Goodarzi
homamajd.bsky.social
Our ENS is vital to gut-brain health. When it breaks down, so does health. Treatments? Almost none.
Access to functional human enteric neurons at scale powers disease modeling and therapeutic discovery. Grateful to everyone who made this possible. www.nature.com/articles/s41...
genophoria.bsky.social
Oh no! I am devastated!
euanashley.bsky.social
Atul Butte died yesterday.
The world lost a giant.
A big bear of a man.
With a huge smile.
With love for everyone.
With energy that could power a room.
I loved everything about Atul.
I loved how he was always happy.
I loved how excited he was about science and helping people.
Reposted by Hani Goodarzi
genophoria.bsky.social
We would especially like to thank all of our colleagues who collaborated with us on this, including @balynzaro.bsky.social and Albertas Navickas, for their contributions to this work. And our funders, including @arcinstitute.org.
genophoria.bsky.social
Finally, we used double-knockdown for in vivo lung colonization assays to confirm the expected epistatic interaction between RBMS3 and TXNIP.
genophoria.bsky.social
We confirmed that TXNIP is correlated with RBMS3, and similarly its expression is associated with better outcomes. Then we looked at TXNIP expression in a cohort of 96 breast cancer samples in-house, stratified by stage, that confirmed reduced expression as disease progresses.
genophoria.bsky.social
To figure out which, if any, of the targets of RBMS3 that we identified are responsible for this phenotype, we performed an in vivo CRISPR screen. Among the targets tested, we found that silencing TXNIP increases metastatic lung colonization.
genophoria.bsky.social
To turn this clinical association into causation, we took advantage of metastasis assays in xenografted mice. We showed that silencing and over-expressing RBMS3 modulates metastasis in vivo in two independent models.
genophoria.bsky.social
Interestingly, this association was most notable in the basal and Claudin-low subtypes of breast cancer, which are known to be aggressive subtypes.
genophoria.bsky.social
We consistently observed that reduced expression of RBMS3 is associated with poor clinical outcomes in breast cancer patients, in multiple datasets.
genophoria.bsky.social
To gain insight into the functional consequences and phenotypic effects of this regulon, we looked at pathways and complexes that may be enriched among the RBMS3 target. We saw a significant enrichment for TGFb and VEGF signaling that are associated with metastatic progression in breast cancer.
genophoria.bsky.social
Finally, we demonstrated the requirement and sufficiency of RBMS3 binding sites for this RBSM3-mediated transcript stabilization. We cloned binding sites from 13 high confidence mRNA targets into a reporter assay, which showed RBMS3-dependent increase in reporter expression.
genophoria.bsky.social
Replacing AUA-carrying mRNAs with these empirical RBMS3 CLIP targets confirmed that RBMS3 direct binding drives transcript stabilization.
genophoria.bsky.social
To show that this effect results from a direct interaction between RBMS3 and its target mRNAs, we performed CLIP-seq (UV crosslinking followed by immuno-precipitation and sequencing). We observed pervasive 3’UTR binding, and also a strong enrichment for the AUA element we had identified.
genophoria.bsky.social
Silencing RBMS3, as expected, resulted in a significant decrease in the stability and expression of the mRNAs that contain AUA-elements in their 3’UTRs.
genophoria.bsky.social
Among these, we chose RBMS3 for further characterization, simply because it was the highest ranking RBP for correlated expression with its putative regulon—identified based on the AUA cis-regulatory element, which was determined by analysis of GreyHound’s sequence importance scores.
genophoria.bsky.social
Applying GreyHound to our breast cancer mRNA stability dataset, we uncovered a network of RBPs associated, and their cognate cis-regulatory elements, as a major determinant of variation in the RNA dynamics of breast cancer.
genophoria.bsky.social
To help decipher the regulatory grammar of context-specific mRNA dynamics, we developed GreyHound: a multimodal deep-learning model that integrates RNA sequences and RNA-binding protein (RBP) expression to predict mRNA stability.